This paper presents a unification and a generalization of the small-gain theory subsuming a wide range of existing small-gain theorems. In particular, we introduce small-gain conditions that are necessary and sufficient to ensure input-to-state stability (ISS) with respect to closed sets. Toward this end, we first develop a Lyapunov characterization of omega ISS via finite-step omega ISS Lyapunov functions. Then, we provide the small-gain conditions to guarantee omega ISS of a network of systems. Finally, applications of our results to partial ISS, ISS of time-varying systems, synchronization problems, incremental stability, and distributed observers are given.